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Updated: Feb 16, 2026
Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various
Miklos Fuzi1, Dora Szabo1, Rita Csercsik1
1Institute of Medical Microbiology, Semmelweis University, Budapest, Hungary.
Abstract:
The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE), emerged by a similar mechanism. The reason(s) why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated.
Insights
Major antibiotic-resistant bacteria, including MRSA, ESBL-producing Klebsiella pneumoniae, and E. coli, gained fitness through mutations conferring fluoroquinolone resistance. This mechanism likely drives the emergence of other multidrug-resistant pathogens like VRE.
Area of Science:
- Microbiology
- Molecular Biology
- Evolutionary Biology
Background:
- Major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae, and ESBL-producing E. coli exhibit enhanced fitness.
- This fitness advantage is linked to high-level resistance to fluoroquinolones.
Purpose of the Study:
- To investigate the mechanisms underlying the favorable fitness balance in major sequence types/lineages of antibiotic-resistant bacteria.
- To review existing information on fitness balance incurred by mutations in DNA gyrase and topoisomerase IV enzymes.
- To present evidence suggesting similar mechanisms drive the emergence of other multidrug-resistant pathogens.
Main Methods:
- Review of available scientific literature on fitness balance associated with mutations in DNA gyrase and topoisomerase IV.
- Analysis of sequence types/lineages of MRSA, ESBL-producing K. pneumoniae, and ESBL-producing E. coli.
- Examination of evidence for similar evolutionary mechanisms in other multidrug-resistant bacteria, such as vancomycin-resistant Enterococcus faecium (VRE).
Main Results:
- Favorable fitness in major sequence types/lineages of these pathogens is primarily achieved through mutations in fluoroquinolone-binding serine residues of DNA gyrase and topoisomerase IV.
- Individual and combined mutations in these enzymes contribute to fitness balance across multiple species.
- Circumstantial evidence suggests vancomycin-resistant Enterococcus faecium (VRE) and potentially other multidrug-resistant bacteria emerge via similar evolutionary pathways.
Conclusions:
- The evolution of specific mutations in DNA gyrase and topoisomerase IV is a key factor in the success of major lineages of fluoroquinolone-resistant MRSA, K. pneumoniae, and E. coli.
- Similar mechanisms are likely responsible for the emergence of other multidrug-resistant pathogens.
- Further research is needed to elucidate why certain pathogen strains are more adept at evolving these advantageous mutations.
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